Approximately 10-20% of women with ductal carcinoma in situ (DCIS) will have recurrent breast cancer, either in situ or invasive, within 5 years of their initial diagnosis. While every year in the U.S. more than 47,000 women are diagnosed with DClS, our ability to accurately predict which patients are most likely to have a recurrence is quite poor. Consequently, treatment decisions are difficult and up to 40% of DCIS patients will have a mastectomy. We propose to conduct a nested case-control study to identify clinical and pathologic factors that could be used to accurately identify DClS patients at high and low risk of a recurrence. The study population will come from the memberships of three Cancer Research Network (CRN) sites, Kaiser Permanente Northern California (KPNC), Kaiser Permanente Southern California (KPSC), and Harvard Pilgrim Health Care (HPHC). DCIS patients diagnosed between 1990 and 2001 and treated with breast-conserving surgery will be identified (N=3,700) and followed for recurrence. Diagnostic slides from patients with a recurrence (N=490) and from matched controls will be retrieved and reviewed by an expert DClS pathologist. One control will be selected for each recurrence (case), matched on health plan, calendar year of the initial diagnosis, age, and follow-up time. Pathology review will be conducted on the slides from the initial and recurrent tumors of cases and from the initial tumors of controls. Data on clinical factors will also be obtained. We aim to do the following: 1) Estimate and compare the risk of recurrence associated with several pathologic features (either alone or combined according to various classification systems) of the index DClS, and compare features of the index DCIS to those in recurrent lesions; 2) Estimate and compare the risk of recurrence associated with several clinical factors, such as age, menopausal status, obesity, and family history of breast cancer; and 3) Evaluate the relation between clinical and pathologic factors, and determine which combination of these factors best identifies subgroups of women at very high and low risk of recurrence. This will be the largest and most comprehensive study to date on prognostic factors for DClS. Our results will provide information on the natural history of this heterogeneous group of lesions, and in the future may help in the development of individually tailored treatment strategies for patients with DCIS.